APP-BP1 Inhibits Aβ42 Levels by Interacting with Presenilin-1

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APP-BP1 Inhibits Aβ42 Levels by Interacting with Presenilin-1

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Title: APP-BP1 Inhibits Aβ42 Levels by Interacting with Presenilin-1
Author: Chen, Yuzhi; Bodles, Angela M; Neve, Rachael L; Mrak, Robert E; Griffin, W Sue T; McPhie, Donna Louise

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Citation: Chen, Yuzhi, Angela M. Bodles, Donna L. McPhie, Rachael L. Neve, Robert E. Mrak, and W. Sue T. Griffin. 2007. APP-BP1 inhibits Aβ42 levels by interacting with Presenilin-1. Molecular Neurodegeneration 2: 3.
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Abstract: Background: The β-amyloid precursor protein (APP) is sequentially cleaved by the β- and then γ-secretase to generate the amyloid β-peptides Aβ40 and Aβ42. Increased Aβ42/Aβ40 ratios trigger amyloid plaque formations in Alzheimer's disease (AD). APP binds to APP-BP1, but the biological consequence is not well understood. Results: We report that when the endogenous APP-BP1 was suppressed by small interfering RNAs (siRNAs), cell-associated Aβ42 was dramatically increased in APP695 expressing primary neurons. The accumulation of Aβ42 was accompanied by significant increases in APP and APP-CTF in APP-BP1 siRNA expressing neurons. In contrast, APP-BP1 overexpression in primary neurons significantly decreased the levels of Aβ and endogenous APP but not APLPs. We also investigated the potential mechanism of APP-BP1-mediated APP processing. APP-BP1 co-precipitated with Presenilin-1 (PS1) in native rat brain extracts, co-migrated with the γ-secretase components in brain membrane extracts in glycerol gradient centrifugation, and colocalized in primary neurons. Further, the endogenous PS1-CTF was significantly downregulated by APP-BP1 expression. Conclusion: Our data suggest that APP-BP1 may inhibit Aβ42 production by interacting with PS1 under physiological conditions.
Published Version: doi:10.1186/1750-1326-2-3
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